The activity of proteolytic enzymes of the elastase type has been implicated in several pathological conditions, for example in arthritis and in pulmonary emphysema. Pharmacological inhibition of an elastase enzyme would be expected to prevent or ameliorate an associated pathological condition. Trifluoromethyl ketone substituted peptide derivatives which are inhibitors of human leukocytic elastase are described in European Patent Application, Publication number 189305 A2.
The present invention relates to certain heterocyclic ketones which are human leukocyte elastase (HLE) inhibitors making them useful whenever such inhibition is desired, such as for research tools in pharmacological, diagnostic and related studies and in the treatment of tissue degenerative diseases such as, for example, pulmonary emphysema in mammals. The invention also includes intermediates useful in the synthesis of these heterocyclic ketones, processes for preparing them, pharmaceutical compositions containing such heterocyclic ketones and methods for their use.